This invention relates to use of lymphotactin as an adjuvant to boost immune response.
The immune response mechanism involves both systemic and localized mucosal responses to pathogens and to vaccines. The response to the immunogen or pathogen may be cell-mediated or humoral. (See Fundamental Immunology, 3rd. edition, (W. E. Paul, Editor), Raven Press, New York,(1993).) For example, many intestinal pathogens require a mucosal immune response to provide effective protection from illness.
The use of an adjuvant as a means of enhancing responses to immunogens has been long known. Adjuvants may function in several ways. Some act on the immune system to elicit a more effective antibody reaction to the antigen by activating host macrophages, dendritic cells, B cells and T cells, or enhancing antigen presentation. Adjuvants may enhance immune responses by prolonging the release of antigen, increasing antigen uptake, up-regulating antigen processing, stimulating cytokine release, stimulating B cell switching and maturation and/or eliminating immuno-suppressor cells. Presently known adjuvants include, aluminum hydroxide and Freund""s complete adjuvant. A list of the most effective adjuvants would include bacterial toxins which may be administered with the target immunogen. Sometimes these immune response-enhancing molecules are bound to the toxin. However, many of these adjuvants cause serious untoward effects.
U.S. Pat. No. 5,571,515 discloses the use of IL-12 as an adjuvant for use to enhance cell-mediated immunity.
There are four classes of chemokines: CC, Cxc3x97C, C and Cxc3x973C. Lymphotactin of the C class of chemokines is similar to CC and Cxc3x97C chemokine families that are common in mammals and that are chemotactic for lymphocytes.
In the adult human, the mucosal surface encompasses more than 300 m2 and requires a significant number of lymphoid cells such as the xcfx84xcex4 T cell receptor (xcfx84xcex4TCR) intraepithelial lymphocytes (IELs), which produce lymphotactin and B cells, which produce secretory immunoglobulin (S-Ig) A antibodies (Abs). S-IgA Abs in the mucosa represent the first line of defense against invading pathogens or toxins that, if left unaltered, lead to pathology. Unfortunately, in the context of vaccine development, attempts to induce these protective Abs has not met with great success.
This invention provides means of enhancing immune response, particularly mucosal immune response, by administration of an immune-enhancing effective amount of lymphotactin in a pharmaceutically acceptable carrier. Lymphotactin may be delivered to the mucosa in conjunction with antigen. Mucosal means of application include oral, intranasal, ocular, intravaginal and/or intraurethral administration in liquid or particulate form.